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Biomedical subjects

T Naito

Publications and source records attributed to T Naito.

At least 181 records · Page 10Linked to original sources

[Glomerular lesion in patients with type II mixed cryoglobulinemia having antibodies to hepatitis C virus].

We report here two cases of mixed cryoglobulinemia showing renal involvement associated with hepatitis C virus (HCV) infection. The subjects were 62- and 63-year-old males. Both patients presented with purpura on the legs, which was diagnosed as allergic vasculitis by skin biopsy. Case 1 followed a clinical course of progressive nephrotic syndrome with mild hematuria. He also had diabetes mellitus and hypertension. In contrast, case 2 showed only mild hematuria without proteinuria at the time of the renal biopsy. Both cases had immunological disarrangements, such as severe hypocomplimentemia and seropositive rheumatic factor. Recently, it was reported that patients with type II mixed cryoglobulinemia had HCV seropositivity, and revealed membranoproliferative glomerulonephritis. These facts strongly suggested that renal lesions are the result of direct damage mediated by cryoglobulinemia and an activated complement pathway through an immune complex mechanism related to HCV.

Antibodies, Viral↗

Adult left isomerism complicated with life threatening arrhythmias detected by the use of biplane transesophageal echocardiography: a case report.

Left isomerism with critical arrhythmia in a 34-year-old housewife is reported. Left isomerism is rare among adult congenital disorders. The prognosis in childhood depends on intractable heart failure, but is unclear in adulthood. We describe an adult patient with left isomerism who recovered from life-threatening arrhythmias. Transesophageal echocardiography was especially useful to identify the morphology of both atrial appendages.

Adult↗

Prevention of proteinuria by the administration of anti-interleukin 8 antibody in experimental acute immune complex-induced glomerulonephritis.

Glomerular infiltration by neutrophils is a hallmark of acute glomerulonephritis. The pathophysiological role of interleukin 8 (IL-8), a potent neutrophil chemotactic cytokine (chemokine), was explored in an animal model of acute immune complex-mediated glomerulonephritis by administering a neutralizing antibody against IL-8. Repeated injection of bovine serum albumin (BSA) into rabbits caused the deposition of immune complexes consisting of BSA and rabbit IgG in glomeruli. Histological analyses revealed a small but significant number of neutrophils in glomeruli and the fusion of epithelial cell foot processes. Concomitantly, urinary levels of protein and albumin increased markedly (3.20 +/- 0.97 and 1.39 +/- 0.53 mg/h, respectively) compared with those of untreated animals (0.77 +/- 0.21 and 0.01 +/- 0.01 mg/h, respectively). Anti-IL-8 antibody treatment decreased the number of neutrophils in glomeruli by 40% and dramatically prevented the fusion of epithelial cell foot process. Furthermore, treatment with anti-IL-8 antibody completely normalized the urinary levels of protein and albumin (0.89 +/- 0.15 and 0.02 +/- 0.01 mg/h, respectively). These results indicated that IL-8 participated in the impairment of renal functions in experimental acute immune complex-mediated glomerulonephritis through activating as well as recruiting neutrophils.

Acute Disease↗

Identification of four metabolites of 3-(phenylamino)alanine, a constituent in L-tryptophan products implicated in eosinophilia-myalgia syndrome, in rats.

3-(Phenylamino)alanine (PAA), a contaminant found in L-tryptophan tablets, has been discussed as a possible cause of eosinophilia-myalgia syndrome (EMS). We administered PAA (100 mg/kg) by gastric gavage to Wistar rats to determine its distribution and metabolism. We developed a purification procedure, using Bond Elut SCX cartridges followed by high performance liquid chromatography (HPLC) in order to determine levels of PAA. The level of PAA in blood was 4.22 micrograms/ml at 5 h and urinary excretion was 21.7 micrograms for 5 h and 84.6 micrograms between 5 and 24 h. The amount of PAA in the contents of the large intestine at 5 h was 0.76 microgram, indicating poor transfer of PAA to the large intestine. However, the highest concentration of PAA was 12.3 micrograms/g in the brain, indicating the passage of PAA through the blood-brain barrier. In addition to detecting PAA in the blood and organs, we also detected four metabolites of PAA in urine. We used gas chromatography mass spectrometry to identify PAA in rat liver, as well as N-(hydroxyphenyl)glycine, N-phenylglycine, 3-(pheylamino)lactic acid, and 3-(hydroxyphenylamino)-lactic acid in rat urine. These results suggest that the degradation pathway of PAA is similar to that of phenylalanine.

Administration, Oral↗

Hepatic injury and lethal shock in galactosamine-sensitized mice induced by the superantigen staphylococcal enterotoxin B.

BACKGROUND/AIMS: Staphylococcal enterotoxin B (SEB) acts as a superantigen binding to class II major histocompatibility complex proteins, and this complex stimulates T cells. The aim of this study was to investigate the pathogenic effects of SEB on hepatic injury and lethal shock in mice. METHODS: SEB was administered to D-galactosamine (GalN)-sensitized mice, and the degree of liver injury and levels of circulating cytokines were determined. In vitro cytokine production in response to SEB was also investigated. RESULTS: Intraperitoneal administration of SEB (50 micrograms) caused lethal shock (50% mortality) associated with massive hepatic necrosis in GalN-sensitized mice, with no mortality on injection of up to 100 micrograms SEB alone. Within 2 hours after injection of SEB, serum tumor necrosis factor alpha (TNF-alpha) levels reached a peak, followed by high levels of serum interferon-gamma (IFN-gamma) up to 10 hours after injection. Passive immunization with anti-TNF-alpha/beta-neutralizing monoclonal antibody (mAb) protected GalN-sensitized mice from the lethal effects of SEB, with less protection with anti-IFN-gamma-neutralizing mAb. SEB induced the production of TNF-alpha and IFN-gamma in a dose-dependent manner from splenic mononuclear cells in vitro. CONCLUSIONS: The results show that SEB contributes to lethal shock associated with severe hepatic injury in GalN-sensitized mice and suggest that TNF-alpha and IFN-gamma produced in response to SEB may be mediators of the lethal toxicity and hepatotoxicity of SEB.

Animals↗

Risk factors for infection and immunoglobulin replacement therapy in adult nephrotic syndrome.

Infection has been recognized as an important cause of morbidity and mortality in children with nephrotic syndrome. However, the incidence and severity of infection and the mechanisms responsible for the increased susceptibility to infection are still unclear in adults. We studied 86 consecutive adult patients with nephrotic syndrome but no diabetic nephropathy. Risk factors for infection were evaluated by logistic regression analysis. Infections were found in 16 patients (19%), of whom six died of infection and two developed end-stage renal failure associated with infection. The relative risk for bacterial infection among patients with serum immunoglobulin G (IgG) levels below 600 mg/dL was 6.74 compared with that for patients with serum IgG levels over 600 mg/dL (95% confidence interval, 1.22 to 36.32; P = 0.029). In patients with serum creatinine levels over 2.0 mg/dL, the relative risk of bacterial infection was 5.31 compared with patients with serum creatinine levels below 2.0 mg/dL (95% confidence interval, 1.08 to 26.09; P = 0.040). Intravenous immunoglobulin (10 to 15 g) was administered prospectively every 4 weeks to 18 patients with serum IgG levels below 600 mg/dL until serum IgG levels increased to over 600 mg/dL. Administration of immunoglobulin resulted in a decreased rate of bacterial infections to a level equal to that in patients with endogenous levels over 600 mg/dL. These data indicate that hypogammaglobulinemia and renal insufficiency are independent risk factors for bacterial infection in adult patients with nephrotic syndrome. The effects of intravenous immunoglobulin suggest that maintenance of serum IgG levels over 600 mg/dL may reduce the risk of infection.

Adult↗

Detection of urinary interleukin-8 in glomerular diseases.

To clarify the mechanism of neutrophil infiltration in glomerulonephritis, both urinary and plasma levels of a potent neutrophil chemotactic cytokine, interleukin-8 (IL-8), were measured in 40 healthy volunteers and 96 patients with various renal diseases. The plasma IL-8 levels were less than 16 pg/ml. The urinary IL-8 levels were elevated in several renal diseases including IgA nephropathy (17 of 43), acute glomerulonephritis (4 of 6), lupus nephritis (11 of 15), purpura nephritis (2 of 4), membranoproliferative glomerulonephritis (1 of 1), and cryoglobulinemia (2 of 2). IL-8 was detected immunohistochemically in diseased glomeruli, suggesting its local production. Elevated urinary IL-8 levels during the acute phase or exacerbations were found to be decreased during spontaneous or steroid pulse therapy-induced convalescence in all patients examined. The urinary IL-8 levels were higher in patients with glomerular leukocyte infiltration than in those without infiltration. Collectively, local production of IL-8 in diseased glomeruli might be involved in the pathogenesis of the glomerular diseases and measurement of IL-8 in the urine might be useful for monitoring the glomerular diseases.

Acute Disease↗

Proliferative response of rabbit and rat gastric epithelial cells to human epidermal growth factor.

The effect of human epidermal growth factor (hEGF) on gastric epithelial proliferation was studied in vitro and in vivo. In the first study, subconfluent gastric epithelial cells derived from fetal rabbit stomach were incubated with hEGF at doses of 0, 1, 10, 50, 100, 500 ng/ml and tritiated thymidine incorporation into DNA was determined. In the second study, fasted rats were given intraperitoneal injections of 100 micrograms/kg hEGF and ornithine decarboxylase activity was quantitated. In the third study, hEGF at doses of 0, 5, 10, 25, 50 micrograms/kg was administered perorally 3 times a day for 7 days. During the experiment, rats were allowed ad libitum intake of food and water. After 7 days, all rats were injected with tritiated thymidine 1 microCi/g body weight and sacrificed 1 h later. Sections from fundic and antral mucosae were processed for autoradiography. While hEGF stimulated tritiated thymidine incorporation into DNA by gastric epithelial cells in vitro, neither parenteral nor peroral administration of hEGF affected the proliferative measurements as assessed by ornithine decarboxylase activity or autoradiography in adult rat gastric fundic and antral mucosae in vivo. These results indicate that although hEGF has a direct proliferative effect on fetal rabbit gastric epithelial cells, exogenously administered hEGF has little effect on adult rat gastric mucosal steady state cell proliferation under physiological conditions.

Animals↗

[The early lesions of renal amyloidosis].

Two patients with minimal amyloid deposition in association with nephrotic syndrome are reported. Since the amyloid deposits in each renal biopsy specimen were inconspicuous, both were first thought to be minimal glomerular changes. A few widely scattered, silver-positive, epimembranous spicules were found on careful reexamination by light microscopy. Congo red stain and electron microscopy confirmed the presence of small glomerular amyloid deposits and amyloid fibrils. Furthermore, immuno-fluorescence microscopy showed partial IgA deposits in the mesangial area and capillary wall. We therefore urge careful examination to detect amyloid deposits of all kidney biopsy specimens of minor glomerular abnormalities, or glomerulonephritis with IgA deposits from elderly patients with nephrotic syndrome. Light microscopy of Congo-red-stained sections and electron microscopy of the fibrillar structure very useful for the detection of small amyloid deposits.

Adult↗

[Study on platelet-derived growth factor (PDGF) and PDGF receptor expression in glomeruli and corticosteroid therapy in IgA nephropathy].

This study was designed to investigate whether expression of platelet-derived growth factor (PDGF) and its receptor in the glomeruli is correlated with clinicopathological parameters in 42 patients with primary IgA nephropathy. Immunohistochemical studies were conducted using frozen sections from biopsy specimens. The intensity of PDGF beta receptor expression in the glomeruli was correlated with the mesangial cell count, but not with clinical parameters, such as daily excretion of urinary protein and creatinine clearance. Moreover, overexpression of PDGF beta receptor in the glomeruli was observed in the patients who were responsive to corticosteroid therapy. These data suggest that PDGF beta receptor expression in the glomeruli of IgA nephropathy could be a useful marker for predicting the prognosis and effectiveness of corticosteroid therapy.

Adult↗

[A case of ANCA-associated rapidly progressive glomerulonephritis with oral aphtha and erythema nodosum].

We reported a case of a 22-year old female with a microscopic form of polyarteritis nodosa (PN) who initially manifested Behçet's disease-like symptoms, such as fever, arthralgia, oral aphtha and erythema nodosum, and rapidly progressive glomerulonephritis (RPGN). On admission, her urinalysis showed active nephritic syndrome and her renal function rapidly deteriorated; serum creatinine levels elevated from 1.2 to 3.9 mg/dl within 2 weeks. Skin biopsy specimens from erythema showed panniculitis. Accordingly, she was treated with daily 30 mg of oral prednisolone and three-day intravenous pulse therapy of 1000 mg of methylprednisolone twice. After treatment, skin eruption and oral aphtha disappeared, and the serum creatinine level improved to 1.2 mg/dl. Percutaneous renal biopsy performed on the 28th day showed focal necrotizing glomerulonephritis and hyalinosis of small arteries. Immunofluorescence studies showed only trace stainings for IgG, IgA and beta lc. Electron microscopic findings revealed fusion of the foot process and swelling of endothelial cells, but no dense deposits. Anti-neutrophil cytoplasmic antibody (ANCA) was positive for IgG class with a 40-fold titer by indirect immunofluorescence test and showed a cytoplasmic pattern combined with high urinary IL-8 level (280.1 pg/ml). We diagnosed this case as a microscopic form of PN. ANCA titer and urinary IL-8 correlated positively with the disease activity, and were finally below 8-fold and 58.6 pg/ml, respectively after resolution of RPGN for 42 months. In this case, ANCA was useful not only for differential diagnosis of the patients with systemic vasculitis and crescentic glomerulonephritis, but also for evaluation of the disease activity.

Adult↗

[A case of life-threatening acute asthma with marked elevation of serum theophylline level during inhalational anesthesia].

A 21-year-old man was admitted to our hospital because of life-threatening acute asthma. His condition deteriorated while he was receiving aminophylline and high-dose corticosterolids, and complicated by pneumomediaststinum. He was intubated and ventilated mechanically. Since peak inspiratory pressure was very high and arterial blood gases were not improving, he was treated with inhaled haltohane and enflurane, and bronchial lavage was done via a bronchoscope. Anesthesia continued for 114 hours before his condition improved. The serum theophylline levels were elevated during anesthesia. Since the dose of aminophylline was not very high, this elevation may have been related to the inhalation of halothane and enflurane.

Acute Disease↗

[A case of idiopathic pulmonary hemosiderosis of adult onset].

A 69-year-old woman suddenly suffered massive hemoptysis and was admitted to the hospital. The test of anti-glomerular basement membrane antibodies was negative. Chest radiograph showed diffuse infiltrative shadows similar to those of lung edema in the both lung fields. The patient's condition worsened gradually during the next 3 weeks, with repeated massive hemoptysis. Steroid pulse therapy had limited effects on the progressive respiratory failure, and the patient died. Autopsy showed alveolar hemorrhage and macrophages containing haemosiderin. Immunofluoresence microscopy showed no deposits of immunoglobulin in the kidney. Idiopathic pulmonary hemosiderosis of adult onset with acute respiratory failure is rare in Japan.

Age of Onset↗

[Empiric therapy with fluconazole in granulocytopenic patients with carcinoma or leukemia].

We performed a randomized clinical trial in granulocytopenic patients with carcinoma or leukemia. Patients with persistent fever for more than 2 days despite antibiotic therapy were randomized to antibiotic plus fluconazole therapy group (FLCZ group) or antibiotic therapy only group (antibiotic group) by the envelope method. It was possible to evaluate clinical efficacies in 62 patients (37 patients in FLCZ group and 25 patients in antibiotics group). In patients whose neutrophil counts were less than 100/microliters on the initial day of therapy, clinical efficacy rates were 72.0% (18/25) in FLCZ group and 57.1% (8/14) in antibiotics group. In patients whose neutrophil counts continued to be less than 100/microliters during therapy, clinical efficacy rates were 64.3% (9/14) and 50.0% (3/6), respectively. Further, in patients whose neutrophil counts continued to be less than 500/microliters during therapy, they were 76.9% (20/26) and 53.3% (8/15), respectively. No severe side effects nor severe case of abnormal change in laboratory test values due to fluconazole were observed in this trial. These data suggest that empiric antifungal therapy with fluconazole is effective for fungal infections in granulocytopenic patients with carcinoma and leukemia.

Adult↗

[Sensitivities to other antiviral drugs and thymidine kinase activity of aciclovir-resistant herpes simplex virus type 1].

Sensitivity tests of various antiviral drugs on aciclovir-resistant strains of herpes simplex virus type 1 (HSV-1) were done in vitro. Activity of thymidine kinase (TK) of the aciclovir-resistant strains was also investigated. A strain of HSV-1 isolated from a patient with herpes labialis was grown in Eagle's minimum essential medium containing 10(-6)M aciclovir (ACV) and passaged 20 times. Then ACV-resistant strains of HSV-1 were obtained. Sensitivity tests of 5 anti-herpetic agents (ACV, ganciclovir, carbocyclic oxetanocin G, (S)-9- (3-hydroxy-2-phosphonylmethoxypropyl)adenine ((S)-HPMPA), and adenine arabinoside (ara-A)) were done on these ACV-resistant strains. The ACV-resistant strains were resistant to ganciclovir and carbocyclic oxetanocin G, but they were sensitive to (S)-HPMPA and ara-A. These ACV-resistant strains showed no detectable TK activity.

Acyclovir↗

Identification of GTP-binding proteins in human glomeruli.

The localization of GTP-binding proteins (G-proteins) in human glomeruli was examined using immunohistochemistry and immunoblotting. Immunohistochemical staining for G-protein subunits demonstrated the existence of Gs alpha, Gi alpha and Go alpha proteins in the glomeruli. Moreover, immunoblots further revealed Gs alpha (52 kD), Gi alpha 1/2 (40-41 kD), Gi alpha 3 (40 kD) and Go alpha (39 kD) in the glomerular membranes. The predominant subspecies of Gs was a 52-kD protein, and Go alpha was detectable in the smallest amounts of the G-protein subunits. However, immunoblots failed to demonstrate detectable amounts of G-proteins in cytosolic extracts. This is the first report that characterizes G-protein subunits in human glomeruli. Further study is required to determine the roles of G-proteins in signal transductions in human glomeruli.

GTP-Binding Proteins↗

Different appearance of gamma delta T cells during salmonellosis between Ityr and Itys mice.

Ity gene, which is believed to be a single gene on proximal mouse chromosome 1, determines susceptibility to Salmonella infection. We have recently demonstrated that the gamma delta T cells specific for purified protein derivative appear at the early stage after infection with Salmonella choleraesuis strain 31N-1 (avirulent strain) in mice. In the present study, we compared the appearance of the gamma delta T cells in Ityr and Itys mice after infection with S. choleraesuis in an attempt to elucidate the role of the gamma delta T cells in the in vivo effect of the Ity locus on murine salmonellosis. The numbers of gamma delta T cells in the peritoneal cavity and liver were significantly larger in DBA/2 (Ityr) mice than those in BALB/c (Itys) mice after infection with a sublethal dose of S. choleraesuis. C.D2 Ityr mice, which are BALB/c mice with Ityr allele, also showed a significant increase in the number of the gamma delta T cells at the early stage after infection. Similar results in different appearances of the gamma delta T cells could be obtained between BALB/c and DBA/2 mice after infection with Mycobacterium bovis, bacillus Calmette-Guérin. The peritoneal adherent cells of DBA/2 mice infected with S. choleraesuis, which expressed a large amount of heat shock/stress protein (hsp) homologous to the mycobacterial 65-kDa hsp, induced significantly higher level of expansion of the peritoneal gamma delta T cells in normal mice in vivo and in vitro than did those of BALB/c mice infected with S. choleraesuis, which expressed a lesser amount of the hsp. These results suggest that the Ity locus may be closely related to the expression of hsp by macrophages after infection with Salmonella, which in turn stimulate the gamma delta T cells in the host during an early phase of salmonellosis.

Animals↗